JP5068763B2 - Lens care composition - Google Patents

Description

  The present invention generally relates to aqueous solutions useful for treating contact lenses. Such a solution is particularly useful as a base for formulating contact lens care products.

In recent years, a multi-purpose solution (MPS) that cleans, disinfects and rinses contact lenses without mechanical rubbing has been developed as a new type of lens care system. Cleaning usually refers to the removal of lipids, proteins and other substances attached to the lens. Disinfection usually refers to the inactivation of harmful bacteria or fungi each time the lens is removed from the eye, usually performed daily. Rinsing usually refers to removing debris from the lens before it enters the eye. These new systems are starting to dominate the majority of the lens care market. Such popularity probably stems from the ease and convenience offered to consumers by these new systems. Since lenses are usually treated with MPS and then used as is without rinsing, MPS exhibits virtually no cytotoxicity, very low irritation, efficient antimicrobial activity and good cleaning efficacy. It is desirable to provide comfort to the lens wearer.

  However, currently available MPSs cannot have all of the desired properties described above. For example, current MPS may not have good efficacy in lipid removal from worn lenses, particularly silicone hydrogel contact lenses that are very susceptible to lipid adhesion and adsorption. In particular, after many cycles of wearing and cleaning with MPS, lipids can accumulate so much that they adversely affect lens performance (eg, vision, comfort, etc.). Furthermore, it would be difficult to maintain (or keep) the cleanliness of the lens as clean as a new lens without mechanically rubbing the worn lens. Deposits (eg, proteins and / or lipids) on the contact lens reduce the light transmission (or transmittance) of the lens, thereby adversely affecting the vision that the lens can provide to the user.

  Therefore, there is a need to develop a multi-purpose lens care solution that has good efficacy in removing lipid from worn lenses, non-existing cytotoxicity, very low irritation, and efficient antimicrobial activity.

SUMMARY OF THE INVENTION Generally, the present invention includes at least one surfactant, polyvinylpyrrolidone (PVP) and xylitol, wherein the combination of polyvinylpyrrolidone (PVP), xylitol and surfactant provides a sustained lipid removal effect. A care composition is provided. The composition of the present invention allows the formulation of a multi-purpose lens care solution to keep the lens clean as substantially clean as a new lens while disinfecting, cleaning and rinsing without rubbing the contact lens. To do.

  The present invention provides the foregoing and other features, and the advantages of the present invention will become more apparent from the following detailed description of exemplary embodiments described herein, read in conjunction with the accompanying drawings. . The detailed description and drawings are merely illustrative of the invention and are not intended to limit the scope of the invention as defined by the claims and their equivalents.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS The present invention can be understood more readily by reading the following detailed description in conjunction with the accompanying drawings, which form a part of this disclosure. Unless defined otherwise, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known in the art and commonly used. Conventional methods such as those provided in the art and various general references are used to perform the disclosed procedures. The present invention is not limited to the specific apparatus, methods, conditions, or parameters described and / or illustrated herein, and the terminology used herein is for the purpose of describing particular embodiments by way of example. It will be understood that the invention is not intended to limit the claimed invention. Also, unless the context clearly indicates otherwise, singular references such as “a”, “an”, and “the” used in the specification, including the claims, include the plural, References to numerical values include at least that specific numerical value. As used herein, a range can be expressed as from “about” or “approximately” one particular value to “about” or “approximately” another particular value. When such a range is expressed, another embodiment includes from the particular value to the other particular value. Similarly, when numerical values are expressed as approximations, by use of “about,” it will be understood that the particular numerical value forms another embodiment.

  The present invention provides a maximum of 70% of the amount of lipid adsorbed by a silicone hydrogel lens (AcuVue® Advance ™) after about 10 cycles of lipid fouling and subsequent cleaning with phosphate buffer. The present invention relates to a lens care composition having a long-lasting lipid removing effect. The present invention is based on the unexpected and beneficial discovery that formulations containing at least a surfactant, polyvinylpyrrolidone (PVP) and xylitol can have a sustained lipid removal effect. Using such a formulation, an aqueous lipid solution (pH about 1) containing FITC-phosphatidylethanolamine (FITC-PE, Molecular Probes) at a concentration of about 0.5 μg / ml (equal to the physiological lipid concentration in tears). 7.0) contaminated contact lenses (AcuVue® Advance ™), this formulation effectively removes lipids from the contaminated lenses. In particular, the amount of lipid adsorbed by silicone hydrogel lenses (AcuVue® Advance ™) decreases or is at least substantially constant after five cycles of fouling and cleaning with the solution of the present invention. The amount of lipid adsorbed by the silicone hydrogel lens (AcuVue® Advance ™) remains clean and can be cleaned with phosphate buffer or Optifree® Express lens MPS disinfection solution (Alcon) After 5 cycles, increase as the number of fouling and cleaning cycles increases.

  The lens care composition of the present invention can be used to clean contact lenses including hard (PMMA) contact lenses, soft (hydrophilic) contact lenses and oxygen permeable hard (RGP) contact lenses. The soft contact lens is a hydrogel contact lens or preferably a silicone hydrogel contact lens.

  “Hydrogel” refers to a polymeric material capable of absorbing at least 10% by weight of water in a fully hydrated state. In general, hydrogel materials are obtained by polymerization or copolymerization of at least one hydrophilic monomer in the presence or absence of additional monomers and / or macromers.

  “Silicone hydrogel” refers to a hydrogel obtained by copolymerization of a polymerizable composition comprising at least one silicone-containing vinyl monomer or at least one silicone-containing macromer.

  As used herein, “hydrophilic” refers to a material or part thereof that is more easily associated with water than lipid.

  “Clean” means that a solution contains one or more active ingredients at a concentration sufficient to loosen and remove loosely held lens deposits and other contaminants on the surface of the article to be cleaned. To do. Although not necessary with respect to the present invention, the user can operate the solution of the present invention with a finger (eg, use a hand to rub the lens with the solution) or an auxiliary device such as a machine that stirs the solution in contact with the lens. You may wish to use it with a cleansing aid.

  In accordance with the present invention, the lens care composition is eye-safe. “Eye-safe” for lens care solutions means that contact lenses treated with the solution are safe to put in the eye without rinsing, that is, the solution is in contact with the eye daily through the contact lens. It means safe and comfortable enough. An ophthalmically safe solution has a tonicity and pH that is compatible with the eye and includes materials and amounts thereof that are non-cytotoxic according to international ISO standards and US FDA regulations.

  “Eye compatible” refers to a solution that can be in close contact with the eye for extended periods of time without significant damage to the eye and without significant user discomfort.

  “Cycle of lipid fouling and subsequent cleaning with a solution” is a process consisting of a fouling step and then a cleaning step, where the fouling step involves a silicone hydrogel lens (AcuVue® Advance ™). The cleaning step is performed by immersing in 1 ml of FITC-phosphatidylethanolamine (FITC-PE) solution (0.5 μg / ml) at 37 ° C. for about 16 hours, and the cleaning step is performed with a lipid-fouling silicone hydrogel lens (AcuVue® Advance). Describes a process carried out by immersing (TM) in 1 ml of a cleaning solution or phosphate buffer for about 8 hours. This cycle simulates lens wear and subsequent lens cleaning with a lens care solution.

  “Persistent lipid removal efficacy” with reference to a lens care solution means that the lens care solution is a silicone hydrogel lens (AcuVue® Advance) even after at least 5 lipid fouling and thereby cleaning cycles. (Trademark)) has the effect of removing lipid adsorbed. Sustained lipid removal efficacy is preferably achieved with a silicone hydrogel lens (AcuVue® Advance) after about 10 cycles of fouling with a lipid fouling solution followed by cleansing under non-abrasive conditions with a lens care solution. The amount of lipid adsorbed by the trademark)) is less than about 70% of the amount of lipid after about 10 cycles of fouling with a lipid fouling solution followed by scrubbing with aqueous phosphate buffer The lipid fouling solution is an aqueous solution containing FITC-phosphatidylethanolamine at a concentration of 0.5 μg / ml. The procedure for performing the fouling and cleaning cycle and the procedure for measuring the amount of lipid adsorbed by the lens is described in Example 6.

  In one embodiment, the present invention comprises at least one surfactant, polyvinyl pyrrolidone (PVP) and xylitol, wherein the surfactant is combined with polyvinyl pyrrolidone (PVP) and xylitol to provide sustained lipid removal efficacy. A silicone hydrogel lens (AcuVue® Advance) that provides a long-lasting lipid removal effect after about 10 cycles of cleansing under conditions of fouling with a lipid fouling solution and subsequent lens care composition. The amount of lipid adsorbed by (trademark) is less than about 70% of the amount of lipid after about 10 cycles of fouling with a lipid fouling solution followed by scrubbing with aqueous phosphate buffer An aqueous solution characterized in that the lipid fouling solution comprises FITC-phosphatidylethanolamine at a concentration of 0.5 μg / ml A lens care composition is provided.

  Any suitable known surfactant can be used in the present invention. Examples of suitable surfactants are poloxamers (Pluronic ™ and Pluronic-R ™) which are nonionic surfactants consisting of block copolymers of propylene oxide and ethylene oxide sold by BASF under the trade name Pluronic. ), Poloxamine which is a block copolymer derivative combining ethylene oxide and propylene oxide with ethylenediamine, tyloxapol which is a 4- (1,1,3,3-tetramethylbutyl) phenol polymer with formaldehyde and oxirane, ethoxylated alkylphenols such as commercial products Various surfactants sold under the name TRITON (Union Carbide, Tarrytown, NY, USA) and IGEPAL (Rhone-Poulenc, Cranbury, NJ, USA), trade name TWEEN (ICI Americas, Inc., Wilmington, Del. , USA.) Polysorbate surfactants sold as Polysorbates such as polysorbate 20, such as polysorbates 20, alkyl glucosides and polyglucosides such as products sold under the trade name PLANTAREN (Henkel Corp., Hoboken, NJ, USA) and polyethoxylation sold under the trade name CREMAPHOR from BASF Including, but not limited to, castor oil.

  Preferred surfactants include polyethylene glycol or polyethylene oxide homopolymers and certain poloxamers such as those from BASF under the trade names PLURONIC® 17R4, PLURONIC® F-68NF, PLURONIC® F68LF and PLURONIC ( There is a substance marketed as (registered trademark) F127, and PLURONIC (registered trademark) F-68NF (National Drug Collection Grade) is most preferable. When present, the poloxamer is about 0.001% to about 5% by weight, preferably about 0.005% to about 1%, more preferably about 0.05% to about 0.6% by weight. Can be used.

  The polyvinylpyrrolidone (PVP) used in the composition of the present invention comprises at least 90% repeat units derived from 1-vinyl-2-pyrrolidone monomer, more preferably at least about 95% such repeat units or A linear homopolymer or an essentially linear homopolymer comprising essentially all and the remainder being selected from polymerization compatible monomers, preferably neutral monomers such as alkenes or acrylates. Alternative names for PVP include povidone, polyvidone, 1-vinyl-2-pyrrolidone and 1-ethenyl-2-pyrrolidone (CAS Registry Number 9003-39-8). The PVP used in the present invention suitably has a weight average molecular weight of about 10,000 to 250,000, preferably 30,000 to 100,000. Such materials are available from various companies, for example from ISP Technologies under the trade name PLASDONE ™ K-29 / 32, from BASF from the United States Pharmacopoeia Grade PVP under the trade name KOLLIDON ™, eg KOLLIDON ™. Sold as K-30 or K-90. Although the present invention is not limited to a specific PVP, K-90 PVP is preferable, and pharmaceutical PVP is more preferable.

  In accordance with the present invention, polyvinylpyrrolidone functions as a lubricant and can provide comfort to the eye. Polyvinylpyrrolidone can be included at up to 2 wt%, preferably from about 0.1 wt% to about 1.0 wt%, more preferably from about 0.2 wt% to about 0.5 wt%.

  Xylitol is a five carbon sugar alcohol found naturally in many plants and fruits. It is non-caloric and has a sweetness quality equivalent to sugar, so it is used as a sweetener in foods such as chewing gum. Xylitol can be used as an isotonic agent for adjusting the tonicity (molar osmotic concentration) of the lens care composition. Xylitol is present in the preferred contact lens care composition of the present invention, advantageously from about 0.4% to about 10% by weight, more preferably from about 1.%, based on the total amount of contact lens care composition formulated as an aqueous solution. It is used in an amount of 0 wt% to about 8 wt%, most preferably 2 wt% to about 6 wt%.

  Surprisingly, it has now been found that the combination of PVP and xylitol with at least one surfactant can have enhanced lipid removal efficacy. This protects against the occurrence of dryness that can lead to tear film loss. The use of a combination of the above active ingredients can also substantially improve comfort when wearing contact lenses. Negative effects caused by surfactants and preservatives are reduced, and contact lens drying is prevented.

  In a preferred embodiment, the lens care solution is a multipurpose solution capable of disinfecting, cleaning and rinsing contact lenses.

  “Disinfectant solution” is effective to reduce or substantially eliminate the presence of various microorganisms present on contact lenses, contact after immersion in a solution or solution having a specific inoculum of microorganisms A solution containing one or more microbicidal compounds that can be tested by closely examining the lens. As used herein, a “disinfectant solution” refers to the possibility that the solution is also useful as a stock solution or that the disinfectant solution may be further useful for daily cleaning, rinsing and storage of contact lenses. Do not exclude.

  Solutions useful for cleaning, chemically disinfecting, storing and rinsing articles such as contact lenses are referred to herein as “multipurpose solutions”. Such a solution may be part of a “multipurpose solution system” or “multipurpose solution package”. A procedure that uses a multipurpose solution, system or package is called a “multifunctional system”. Multipurpose solutions can be used by some wearers, such as those who are particularly sensitive to chemical disinfectants or other drugs, to rinse or wet the contact lens with another solution, such as sterile saline, prior to lens insertion. Do not exclude the possibility of preferring to do. “Multipurpose solutions” also do not exclude the possibility of regular detergents that are not used daily or supplementary detergents, such as enzyme detergents, to remove proteins that are usually used once a week.

  The disinfecting solution of the present invention can be used to disinfect contact lenses against a wide range of microorganisms including Fusarium solani, Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens and Candida albicans. In line with the spirit of the present invention, “disinfection” refers to making virtually all pathogenic microorganisms in a growing state, including gram-negative and gram-positive bacteria and fungi, unable to grow. Compounds and compositions that inactivate such pathogenic microorganisms are known as microbicides.

  The disinfectant or MPS solution of the present invention must contain a microbicide at a concentration sufficient to effect the desired disinfection of the contact lens. The specific concentration required for a microbicide useful in the present invention must be determined empirically for each microbicide. Some of the factors that affect the effective concentration are the specific activity of the microbicide against the specified pathogen, the molecular weight of the microbicide, and the solubility of the microbicide. It is also important that the selected microbicide is used at a concentration that is physiologically tolerated. The list of microbicides that can be used in the present invention includes biguanides, biguanide polymers, their salts, N-alkyl-2-pyrrolidones, polyquaternium-1, bronopol, benzalkonium chloride and hydrogen peroxide, It is not limited to these. Currently useful antimicrobial biguanides include biguanides, biguanide polymers, their salts and mixtures thereof. Preferably, the biguanide is selected from alexidine free base, alexidine salt, chlorhexidine free base, chlorhexidine salt, hexetidine, hexamethylene biguanide and their polymers and salts thereof. Most preferably, the biguanide is a hexamethylene biguanide polymer (PHMB), also called polyaminopropyl biguanide (PAPB).

  A typical solution of the present invention contains about 0.01 to about 10 ppm, preferably about 0.05 to about 5 ppm, more preferably about 0.1 to about 2 ppm, and even more preferably about 0.0. It is contained in an amount of 2 to about 1.5 ppm.

  PHMB has a broad spectrum of activity and non-specific mechanism of action against bacteria, but may cause some level of corneal staining (Jones Lyndon, et. Al. "Asymptomatic corneal staining associated with the use of balafilcon silicon-hydrogel contact lenses disinfected with a polyaminopropyl biguanide-preserved care regimen ", Optometry and Vision Science 79: 753-61 (2002)). Therefore, it would be desirable to reduce the amount of PHMB in the lens care solution while maintaining the antimicrobial efficacy of the lens care solution. The addition of PVP, cellulose ether and xylitol does not negatively affect the antimicrobial efficacy of the antiseptic solution, and does not negatively affect the toxicity of PHMB present in the contact lens care composition of the present invention. Research has shown that microbiological efficacy can be increased. The concentration of PHMB can be reduced to about 0.5 ppm.

  When the lens care composition comprises a biguanide or biguanide polymer (PHMB) as a microbicide, it preferably contains less than 1000 ppm, more preferably less than 500 ppm, and even more preferably less than 100 ppm chloride ions. A 0.6% sodium chloride solution, probably close to the concentration of sodium chloride in the eye, will give about 3600 ppm chloride ions in the solution. Such a high concentration of chloride ions will reduce the antimicrobial effectiveness of PHMB, especially those with less than 0.5 ppm PHMB.

  The composition preferably includes an effective amount of a chelating component. Ethylenediaminetetraacetic acid (EDTA), its salts and mixtures thereof are particularly effective, but any suitable, preferably ophthalmically acceptable chelating component can be included in the composition. EDTA is a low level non-irritating chelating agent that can exert a synergistic effect with PHMB to increase antimicrobial efficacy. Typical amounts of EDTA are from about 0.001% to about 1%, preferably from about 0.002% to about 0.5%, more preferably from about 0.001% to about 1%, based on the total amount of the contact lens care composition. It is 0.004 wt% to 0.1 wt%, more preferably about 0.005 wt% to about 0.05 wt%.

The composition of the present invention preferably contains a buffer. The buffer preferably has a physiologically acceptable pH, preferably in the desired range, eg about 6.3 to about 7.8, preferably 6.5 to 7.6, more preferably 6.8 to 7.4. Keep in range. Physiologically compatible known buffers can be used. Suitable buffering agents as components of the contact lens care compositions of the present invention are known to those skilled in the art. Examples are boric acid, borates such as sodium borate, citric acid, citrates such as potassium citrate, bicarbonates such as sodium bicarbonate, tris (trometamol, 2-amino-2-hydroxymethyl-1 , 3-propanediol), bisamino polyols, phosphate buffers such as Na ₂ HPO ₄ , NaH ₂ PO ₄ and KH ₂ PO ₄ or mixtures thereof. The amount of each buffer is such that it is necessary to have the effect of achieving the desired pH of the composition. Usually included in an amount of 0.001% to 2% by weight, preferably 0.01% to 1% by weight, and most preferably about 0.05% to about 0.30% by weight.

  Preferred buffering agents are those of formula (I)

Wherein a, b, c, d, e, f, g and h are each independently an integer of 1 to 6, and R and R ′ are independently -H, -CH ₃ , - (CH _{2) 2-6} -H and - (CH ₂₎ is selected from the group consisting of _1-6 -OH)
This is a bisamino polyol. In the present invention, the buffer represented by formula (I) can be provided in the form of various water-soluble salts. The most preferred bisaminopolyol is 1,3-bis (tris [hydroxymethyl] methylamino) propane (bis-trispropane).

  Bis-trispropane shows a synergistic effect with certain microbicides (eg PHMB) and fungicides, resulting in significantly higher microbicidal activity than the same active ingredient used with other buffers. It turns out that it can be generated. Bis-trispropane is described under the biological buffer of Biochemicals and Reagents, Sigma-Aldrich Co., 2000-2001 edition. The specific structure of bis-trispropane is shown in Formula II.

The dissociation constants of this dibasic compound are pKa ₁ = 6.8 and pKa ₂ = 9.5, which makes an aqueous solution of this compound useful as a buffer in a wide pH range of about 6.3 to 9.3. To do. The concentration of bis-trispropane used in the present invention is harmless to the eye and known contact lens materials and is therefore compatible with the eye.

  Preferably, the solution of the present invention has a low concentration of phosphate ions and is preferably substantially free of phosphate ions. It has been surprisingly found that solutions having a total of less than 1500 ppm of phosphate and chloride ions are effective against a broad spectrum of microorganisms including C. albicans. Known solutions generally have very high concentrations of phosphate ions and chlorides due to the use of a large amount of phosphate buffer, sodium chloride or potassium chloride isotonic agents and hydrochloric acid or phosphate to adjust the pH low. It had thing ion.

  The solution of the present invention can optionally contain dexpantenol. Dexpantenol is an alcohol of pantothenic acid, also called provitamin B5, D-pantothenyl alcohol or D-panthenol. Dexpantenol is present in the solution of the present invention in an amount of 0.005% to 10%, particularly 0.01 to 5%, preferably 0.01 to 1%, more preferably 0.01 to 0%. It can be used in an amount of .5%, most preferably in an amount of about 0.01-0.25%.

  In addition to the above components, the contact lens care composition of the present invention generally has one or more other components such as an isotonic agent (a substance that affects tonicity) acceptable to the eye other than xylitol, a thickening agent. Contains agents. Although generally unnecessary, an enzyme cleaning material may be included in the contact lens care product of the present invention. The amount of these or other conventional additives used in the contact lens care compositions of the present invention can be varied within a range known to those skilled in the art.

  Contact lens care products are usually formulated in a manner that makes them isotonic with tear fluid. A solution that is isotonic with tear fluid is generally understood to be a solution whose concentration corresponds to a 0.9% sodium chloride solution. Deviations from this concentration are possible as long as the contact lens being processed is not damaged.

  Tonicity with tears or other desired tonicity can be adjusted by adding xylitol and optionally organic or inorganic substances that affect tonicity. Suitable tonicity agents that are acceptable to the eye include, but are not limited to, sodium chloride, potassium chloride, glycerol, mannitol, sorbitol, and mixtures thereof. The tonicity of the solution is usually adjusted to be in the range of about 200 to about 450 milliosmol (mOsm), preferably about 200 to 450 mOsm, preferably about 250 to 350 mOsm.

  In accordance with the present invention, the solution of the present invention is optionally preferably a cellulose ether, more preferably methylcellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose, hydroxypropylmethylcellulose (HPMC). ) Or a mixture thereof. More preferably, the cellulose ether is hydroxyethylcellulose (HEC), hydroxypropylmethylcellulose (HPMC) or a mixture thereof. The cellulose ether is from about 0.01% to about 5%, preferably from about 0.05% to about 3%, more preferably from about 0.1% by weight, based on the total amount of the contact lens care composition. Present in the composition in an amount of about 1% by weight. It is believed that cellulose ether can be used to increase the viscosity of lens care and can act as a lubricant in lens care compositions.

  The solution is compatible with both hard and soft lenses and can be used with virtually any known disinfection technique, including “cold” immersion under ambient temperature conditions and high temperature disinfection methods. . The disinfecting solutions of the present invention are particularly noteworthy with respect to very low toxicity with a broad spectrum of bactericidal and fungicidal activity at low concentrations and reduced affinity for binding and concentration when used with soft contact lenses.

  The contact lens care compositions of the present invention are suitable for all types of contact lenses. This includes in particular so-called hard contact lenses and soft contact lenses, as well as so-called hard flexible or oxygen permeable contact lenses. The contact lens care composition of the present invention has a cleaning action, and in addition, in some cases has an antimicrobial action.

  The contact lens care compositions of the present invention are prepared in a known manner, in particular by mixing the ingredients with water or dissolving the ingredients in water in a conventional manner.

An aqueous solution containing the following components has been found to be particularly useful for cleaning and disinfecting contact lenses.
Poloxamer 0.005% to 1%
PVP 0.01% ~ 1%
Xylitol 1% -8%
PHMB Less than 1.5ppm EDTA Less than 0.1% Bis-Trispropane 0.001% to 2%

More preferred is a solution having the following components.
Poloxamer 0.05% -0.4%
PVP 0.05% -0.5%
Xylitol 2% -6%
PHMB Less than 1.2ppm EDTA 0.001% to 0.006%
Bis-trispropane 0.05% to about 0.30%

  The composition according to the invention is particularly suitable for cleaning and possibly disinfecting contact lenses. The contact lens care composition of the present invention is used in a known manner, for example, by contacting the contact lens with the contact lens care composition for a period sufficient to clean or disinfect the contact lens. Depending on the lens type and degree of fouling, a sufficient time of several minutes to about 24 hours, preferably about 1 to about 12 hours, more preferably about 2 to about 8 hours, and even more preferably about 4 to about 12 hours. The range proved feasible.

  The contact temperature is preferably in the range of about 0 ° C to about 100 ° C, more preferably about 10 ° C to about 60 ° C, more preferably about 15 ° C to about 37 ° C. Contact at or near ambient temperature is very convenient and useful. Contact preferably occurs at or near ambient pressure.

  When the lens care solution is a multipurpose solution, contact preferably occurs for a period of about 5 minutes or a range of about 1 hour to about 12 hours or more. Particularly preferred is a solution having a PHMB of 0.5 ppm or less and having a logarithmic decay rate of at least one C. albicans within 15 minutes from contact with the lens. Also preferred is having a PHMB of less than 0.25 ppm and obtaining a logarithmic decay rate of at least 1.0, more preferably 1.5 C. albicans within 15 minutes, more preferably within 30 minutes. A solution that obtains a logarithmic decay rate of at least 2.0 for albicans.

  The contact lens can be brought into contact with the solution by immersing the lens in the solution. Although not required, the solution containing the contact lens can be agitated, for example, by shaking the container containing the solution and the contact lens, to at least facilitate removal of deposits from the lens.

  In another aspect, the present invention provides a method for cleaning and / or disinfecting contact lenses. The method includes contacting one or more contact lenses with a contact lens care composition of the present invention for a period of time sufficient to clean and / or disinfect the one or more contact lenses.

  Since the solution of the present invention does not have a negative effect on the proteolytic activity of an enzyme such as UNIZYME®, the solution and method of the present invention together with an enzyme for removing debris or deposits from contact lenses. It can also be used. After such a contact step, the contact lens may optionally be rubbed by hand with saline or rinsed without rubbing to remove additional deposits from the lens. The cleaning method can also include rinsing the lens to substantially remove the liquid aqueous medium prior to returning the lens to the wearer's eye.

  In a further aspect, the present invention provides a kit for cleaning and / or disinfecting contact lenses. The kit includes a bottle containing the lens care solution, from which the lens care solution is long enough for the lens care solution to clean and / or disinfect one or more contact lenses and their contact lenses. For a period of time, the lens care solution comprises at least one surfactant, polyvinyl pyrrolidone (PVP), xylitol, and a buffer, where the surfactant is polyvinyl pyrrolidone (PVP). In combination with xylitol to provide a lasting lipid removal effect, which lasts about 10 cycles of cleansing under lipid fouling solution fouling followed by non-rubbing conditions with a lens care solution. Later, the amount of lipid adsorbed by the silicone hydrogel lens (AcuVue® Advance ™) The lipid fouling solution is characterized by not more than about 70% of the lipid content after about 10 cycles of fouling with a lipid fouling solution followed by scrubbing with aqueous phosphate buffer. An aqueous solution containing phosphatidylethanolamine at a concentration of 0.5 μg / ml.

  The kit optionally includes instructions that show how to clean and / or disinfect the contact lens using one or more lens care cases and / or lens care solutions for treating the contact lens.

  The above disclosure enables one skilled in the art to practice the invention. In order to allow the reader to better understand the specific implementation and its advantages, it is recommended to refer to the following examples.

Example 1
An aqueous solution having the composition shown in Tables 1a and 1b in purified water was prepared.

Example 2
This example illustrates various tests for cytotoxicity of the lens care solution prepared in Example 1.

alimarBlue ™ reduction assay
Cell viability in the presence of the lens care solution prepared in Example 1 was assayed according to BioSource International's alamarBlue ™ reduction assay. Either L929 cells or HCE-T cells were used for the study. The test mixture was prepared by diluting the lens care solution with an equal volume of growth medium (50% dilution). The alamarBlue ™ reduction was then measured fluorometrically at 24 hours.

Neutral red based test
Cell viability in the presence of the lens care solution prepared in Example 1 was assayed according to the SIGMA® neutral red based in vitro toxicology assay. Either L929 cells or HCE-T cells were used for the study. The test mixture was prepared by diluting the lens care solution with an equal volume of growth medium (50% dilution). At 24 hours, the absorbance near 540 nm was measured spectrophotometrically.

US Pharmacopoeia Dissolution Test The cytotoxicity of lens care solutions was evaluated using a standard US Pharmacopoeia dissolution test ("Biological Reactivity Tests, in vitro: Elution Test", USP). The lens care solution was diluted with serum supplemented cell medium to a 25% test solution concentration. After 48 hours, each culture was examined microscopically for the presence of morphological changes, cell density reduction or cell lysis induced by the test solution using trypan blue. All solutions 10-12 prepared in Example 1 passed the United States Pharmacopeia dissolution test.

ISO eye irritation test The solution 12 prepared in Example 1 was tested for irritation to rabbit eye tissue according to the ISO eye irritation test protocol. No stimulatory effect was seen for solution 12.

  Table 2 shows the results of cell viability in the presence of the lens care solution of the present invention.

Example 3
In order to evaluate the disinfection performance (microbial efficacy) of the solution prepared according to Example 1, Fusarium solani, C. albicans, Serratia marcescens, S. aureus A series of tests were performed on (S. aureus) and P. aeruginosa. The inoculation level for each test was 1.0 × 10 ^{5 to} 1.0 × 10 ⁶ cfu / ml. At least two inoculums were used for each organism and the results obtained were averaged as shown in Table 3.

Example 4
In order to evaluate the disinfection performance (microbial efficacy) of the solution prepared according to Example 1, after long-term storage at 80 ° C., Fusarium solani, C. albicans, Serratia marset A series of tests were performed on Sense (S. marcescens), S. aureus and P. aeruginosa. The inoculation level for each test was 1.0 × 10 ^{5 to} 1.0 × 10 ⁶ cfu / ml. At least two inoculums were used for each organism and the results obtained were averaged as shown in Table 4.

Example 5
CIBASOFT (registered trademark) (CIBA Vision), FOCUS (registered trademark) 1-2 WEEK LENSES (registered trademark) (CIBA Vision), FreshLook (registered trademark) (CIBA Vision), FOCUS ( Compatibility with registered trademarks NIGHT & DAY (registered trademark) (CIBA Vision), O2OPTIX (registered trademark) (CIBA Vision), AcuVue (registered trademark) 2, AcuVue (registered trademark) Advance (registered trademark), PureVision (registered trademark) A series of tests were conducted to evaluate. After repeated treatment of these lenses with the solution, it was found that no significant differences in lens parameters such as diameter, base curve and center thickness were found. The solution was compatible with the lens tested.

Example 6
This example describes a procedure for testing the lipid removal efficacy of a lens care solution (ie, the ability of a lens care solution to remove lipid from a lens). Divide the lens under test into three groups-test lens, control lens and standard lens. The test lens is first immersed in a solution of fluorescently labeled lipid (eg, FITC-phosphatidylethanolamine (FITC-PE) from Molecular Probes) for a period of time and then immersed in a lens care solution for another period of time. Control lenses are immersed in phosphate buffered saline (PBS) and not treated with lens care solution. A standard lens is dipped into a solution of FITC-PE of known concentration to establish a standard curve for determining FITC-PE concentration. The experimental procedure is as follows.

1. Each lens is equilibrated overnight in 1 ml PBS in one of the holes of a 24-well polystyrene plate.
2. Using 24-well polystyrene plates, place each test lens in FITC-phosphatidylethanolamine (FITC-PE) at 0.5 μg / ml (equal to physiological concentration) in one well at 37 ° C. Soak for 16 hours. Each control lens (same lens) is immersed in 1 ml PBS. The number of test lenses and control lenses is preferably 5.
3. Also on the same day, one lens (same as test lens and control lens) and FITC-phosphatidylethanolamine in any concentration ranging from 0 to 1 ug / ml (eg, 1, 0.5, 0.25). , 0.125, 0.0625 and 0 ug / ml) should be prepared for standard curve plates. Preferably, two lenses are used for each density point. These lenses are left at 37 ° C. for a constant temperature.
4. After 16 hours immersion, rinse the test and control lenses 3 times each using 1 ml PBS. All lenses are transferred to holes in a 24-well plate, each containing 1 ml PBS for each lens, and fluorescence is measured using a plate reader (eg, Wallac). These lenses are called day 0 lenses. A standard curve plate is run in the same manner. A “standard curve plate” is run on the day of a given sample / control plate run. The lens in the “standard curve plate” should not be rinsed, transferred, and kept in its original hole.
5. All test lenses are transferred to a 24-well plate containing 1 ml of lens care solution and placed for 8 hours. The control lens is immersed in PBS for the same 8 hours. Put these on the bench.
6). Each lens is rinsed 3 times using 1 ml of PBS each time and then transferred to a fresh plate containing PBS. Measure fluorescence in both sample / control plate and standard curve plate. These are called day 1 lenses.
7). The lenses are placed in holes containing 1 ml of fresh 0.5 ug / ml FITC-PE solution (for test lenses) or 1 ml of fresh PBS (for control lenses). These lenses are soaked overnight (16 hours) at 37 ° C. and such a cycle is continued for 5 days, 7 days or 2 weeks.
Take fluorescence readings on day 8.0, day 1, day 5, day 7, day 10 and day 14. Calculate lipid concentration based on specific standard curve readings. Compare the amount of lipid absorption on the lens after cleaning with lens care solution over the cycle period.

Example 7
The lipid removal efficacy of the lens care solution (Solution 12) was tested in comparison with Alcon's Optifree® Express, using phosphate buffer without rubbing. Acuvue® Advance ™ was used as a commercially available silicone hydrogel contact lens.

  Alcon's Optifree® Express MPS disinfection solution includes citrate, Tetronic 1304 (tetrafunctional block copolymer based on ethylene oxide and propylene oxide), AMP-95 (aminomethylpropanol), sodium chloride, boric acid, sorbitol, Contains AMP-95, disodium edetate, 0.001% Polyquad (R) ** (polyquaternium-1) and 0.0005% Aldox (R) ** (Myristamidopropyldimethylamine).

  A lipid removal efficacy test was performed according to the procedure described in Example 6. The results are shown in FIG. Column 1 represents the lipid concentration in the lens before and after the number of cycles (lipid soak and clean with solution 12) and column 2 represents the cycle (clean with lipid soak and Optifree® Express MPS disinfectant). The lipid concentration in the lens before and after the number of times is represented, and column 3 represents the lipid concentration in the lens before and after the number of cycles (lipid soaking and cleaning with phosphate buffer). The results show that the lens care solution of the present invention has better lasting cleaning efficacy in lipid removal than Alcon's Optifree® Express MPS disinfectant solution. The solution of the present invention can maintain the lipid concentration in the lens at a much lower level than the Optifree® Express MPS disinfectant solution after 10 cycles of fouling (use of simulated lens) and cleaning. it can. When lenses are cleaned using the solutions of the present invention, intralipid lipid levels remain substantially constant or slightly decrease. In contrast, when lenses are cleaned using Alcon's Optifree® Express MPS disinfectant solution, the lipid level in the lens gradually increases as the number of fouling (use of simulated lenses) and cleaning cycles increases. To increase.

  Although various embodiments of the invention have been described using specific terms, apparatus, and methods, such description is for illustrative purposes only. The words used are for explanation purposes and not for limitation. It will be understood that variations and modifications can be effected by a person of ordinary skill in the art without departing from the spirit or scope of the invention as set forth in the claims. In addition, it should be understood that the various embodiments may be interchanged in whole or in part. Furthermore, titles, headings, etc. are provided to enhance the understanding of the reader of this document and should not be read as limiting the scope of the present invention. Accordingly, the essence and scope of the claims should not be limited to the description of the preferred embodiments contained herein.

The amount of lipid adsorbed by a silicone hydrogel contact lens (AcuVue® Advance ™) is shown as a function of the cycle number of simulated wear and non-rubbing cleansing with the lens care solution.

Claims (24)

A lens care aqueous solution comprising at least one surfactant, polyvinylpyrrolidone (PVP), xylitol and a buffer, wherein the lens care solution has a pH of 6.3 to 7.8 ;
A surfactant, in combination with polyvinylpyrrolidone (PVP) and xylitol, provides a sustained lipid removal effect;
A silicone hydrogel lens (AcuVue (R) Advance (TM)) with a lasting lipid removal effect after about 10 cycles of fouling with a lipid fouling solution and subsequent cleaning under non-abrasive conditions with a lens care solution The amount of lipid adsorbed by is about 70% or less of the amount of lipid after about 10 cycles of fouling with a lipid fouling solution followed by scrubbing with aqueous phosphate buffer. age,
A contact lens care aqueous solution, wherein the lipid fouling solution is an aqueous solution containing FITC-phosphatidylethanolamine at a concentration of 0.5 μg / ml.   The amount of lipid adsorbed by the silicone hydrogel lens after about 10 cycles of fouling with a lipid fouling solution and subsequent cleaning under non-abrasive conditions with the lens care composition is the result of fouling by the lipid fouling solution and subsequent aqueous The contact lens care aqueous solution according to claim 1, wherein the aqueous solution is less than about 50% of the lipid amount after about 10 cycles of cleaning under non-rubbing conditions with a phosphate buffer.   The at least one surfactant is a nonionic surfactant comprising a block copolymer of propylene oxide and ethylene oxide, and the polyvinyl pyrrolidone contains at least 90% of repeating units derived from 1-vinyl-2-pyrrolidone monomer. The aqueous contact lens care solution according to claim 1, which is a linear or essentially linear homopolymer. The aqueous contact lens care solution of claim 3, wherein the block copolymer of propylene oxide and ethylene oxide is included in an amount of about 0.005 wt% to about 1 wt%. The buffer is of the formula (I)

Wherein a, b, c, d, e, f, g and h are each independently an integer of 1 to 6, and R and R ′ are independently -H, -CH ₃ , - (CH _{2) 2-6} -H and - (CH ₂₎ is selected from the group consisting of _1-6 -OH)
The contact lens care aqueous solution of Claim 3 containing the bisamino polyol or its salt.   The contact lens care aqueous solution according to claim 5, wherein the bisaminopolyol is 1,3-bis (tris [hydroxymethyl] methylamino) propane (bis-trispropane).   The aqueous contact lens care solution of claim 3, wherein polyvinylpyrrolidone is included in an amount of about 0.1 wt% to about 1.0 wt%.   The aqueous contact lens care solution of claim 3, wherein xylitol is included in an amount of about 1.0 wt% to about 8 wt%. Xylitol is included in an amount of about 2% to about 5% by weight, polyvinylpyrrolidone is included in an amount of about 0.1% to about 0.4% by weight, and a block copolymer of propylene oxide and ethylene oxide is about 0 %. The contact lens care aqueous solution of claim 3, which is included in an amount of 0.005 % to about 1 % by weight.   The contact lens care aqueous solution according to claim 3, further comprising a polymer antimicrobial agent.   The contact lens care aqueous solution according to claim 10, wherein the polymer antimicrobial agent is PHMB.   12. The aqueous contact lens care solution of claim 11, wherein the concentration of PHMB is from about 0.05 to about 5 ppm.   12. The aqueous contact lens care solution of claim 11, wherein the PHMB concentration is about 0.1 to about 2 ppm.   The contact lens care aqueous solution according to claim 13, wherein the PHMB concentration is less than 1.5 ppm and contains less than 1000 ppm of chloride ions.   15. The aqueous contact lens care solution of claim 14 having a tonicity of about 200 to about 450 milliosmol (mOsm).   15. The aqueous contact lens care solution of claim 14, further comprising a chelating agent.   The contact lens care aqueous solution according to claim 16, wherein the chelating agent is EDTA. (A) from about 0.005% to about 1% by weight of a block copolymer of propylene oxide and ethylene oxide ;
(B) about 0.01% to about 1% by weight of polyvinylpyrrolidone,
(C) about 1% to about 8% xylitol,
(D) PHMB less than 1.5 ppm,
(E) about 0.001% to 2% by weight of a buffer, and (f) about 0.001% to about 1% by weight of EDTA.
A multi-purpose contact lens solution is an aqueous solution containing said solution has a pH of tonicity and 6.3 to 7.8 of 200~450mOsm / kg, multipurpose contact lens solution.   The amount of lipid adsorbed by a silicone hydrogel lens (AcuVue® Advance ™) after about 10 cycles of fouling with a lipid fouling solution and subsequent cleaning under non-abrasive conditions with a multi-purpose contact lens solution Is about 70% or less of the amount of lipid after about 10 cycles of fouling with a lipid fouling solution followed by scrubbing with aqueous phosphate buffer 19. The multipurpose contact lens solution according to claim 18, wherein the lipid fouling solution is an aqueous solution containing FITC-phosphatidylethanolamine at a concentration of 0.5 [mu] g / ml. The at least one surfactant is a nonionic surfactant comprising a block copolymer of propylene oxide and ethylene oxide, and the polyvinyl pyrrolidone contains at least 90% of repeating units derived from 1-vinyl-2-pyrrolidone monomer. A linear or essentially linear homopolymer, wherein the buffer is of the formula (I)

Wherein a, b, c, d, e, f, g and h are each independently an integer of 1 to 6, and R and R ′ are independently -H, -CH ₃ , - (CH _{2) 2-6} -H and - (CH ₂₎ is selected from the group consisting of _1-6 -OH)
The multipurpose contact lens solution according to claim 19, comprising a bisaminopolyol or a salt thereof.   The amount of lipid adsorbed by the silicone hydrogel lens after about 10 cycles of fouling with a lipid fouling solution and subsequent cleaning under non-abrasive conditions with the lens care composition is the result of fouling by the lipid fouling solution and subsequent aqueous 21. The multipurpose contact lens solution of claim 20, wherein the multipurpose contact lens solution is about 50% or less of the lipid content after about 10 cycles of cleaning under non-rubbing conditions with a phosphate buffer.   21. A multipurpose contact lens solution according to claim 20, wherein the bisaminopolyol is 1,3-bis (tris [hydroxymethyl] methylamino) propane (bis-trispropane) and the chelating agent is EDTA.   A kit for cleaning and / or disinfecting a contact lens, comprising a bottle containing a lens care solution, wherein the lens care solution is removed from the bottle, wherein the lens care solution comprises one or more contact lenses and their The lens care solution can be dispensed into a contacting container for a length of time sufficient to clean and / or disinfect the contact lens, and the lens care solution comprises at least one surfactant, polyvinylpyrrolidone (PVP), xylitol And a buffering agent, in combination with polyvinylpyrrolidone (PVP) and xylitol, to provide a sustained lipid removal effect, which can be sustained by a lipid fouling solution and subsequent lenses Silicone hydrogel lens (A) after about 10 cycles of cleaning under non-rubbing conditions with the care solution The amount of lipid adsorbed by cuVue® Advance ™) is the amount of lipid after about 10 cycles of fouling with a lipid fouling solution followed by scrubbing with aqueous phosphate buffer. The lipid fouling solution is an aqueous solution containing FITC-phosphatidylethanolamine at a concentration of 0.5 μg / ml.   A method of cleaning and / or disinfecting a contact lens comprising the step of contacting one or more contact lenses with a contact lens care solution for a period of time sufficient to clean and / or disinfect the one or more contact lenses. The lens care solution is in a container that is in contact with the lens care solution from the bottle for a period of time sufficient to clean and / or disinfect one or more contact lenses. The lens care solution comprises at least one surfactant, polyvinylpyrrolidone (PVP), xylitol and buffer, and the surfactant in combination with polyvinylpyrrolidone (PVP) and xylitol, Providing a long-lasting lipid removal effect. The amount of lipid adsorbed by the silicone hydrogel lens (AcuVue® Advance ™) after about 10 cycles of cleaning under non-rubbing conditions with the lens care solution is reduced by the lipid fouling solution. And about 70% or less of the amount of lipids after about 10 cycles of cleaning under non-rubbing conditions with aqueous phosphate buffer, and the lipid fouling solution contains 0% FITC-phosphatidylethanolamine. A method which is an aqueous solution containing a concentration of 5 μg / ml.

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